Organo bismuth biocide



l, ilrfwll iil a a) 55) lg, tl/t/ 3,239,411 ORGANO BISMUTH BIOCIDE John R. Leebrick, Roselle Park, N.J., assignor, by mesne assignments, to M & T Chemicals Inc., New York, N .Y., a corporation of Delaware N0 Drawing. Filed June 14, 1962, Ser. No. 202,377 22 Claims. (Cl. 167-30) This invention relates to methods of preventing and/ or inhibiting the growth of bacteria and/or fungi and to compositions of matter utilized in these methods. The invention also relates to materials which have been made resistant to attack by bacteria and/ or fungi by the aforesaid methods.

It is an object of this invention to provide methods for inhibiting and/or preventing the growth of-baeterial It is also an object of this invention to provide methods for inhibiting and/or preventing the growth of fungi. The invention also contemplates providing compositions which are useful in the aforesaid methods as the source of the active bactericidal and/or fungicidal compound(s). It is still another object of the invention to provide bacteria and/ or fungi resistant paints. The invention further contemplates the provision of bacteria and/or fungi resistant plastics, and fibrous products such as textiles and paper products. It is also an object of this invention to provide sanitizer compositions having particular utility in hospital treatment.

The present invention contemplates the prevention and/or inhibition of growth of bacteria and fungi by applying to the locus to be protected, an active amount of at least one bismuth compound having the formula R' BiX or R BiX wherein n is l or 2, R is an aryl group, and R is an alkyl, cycloalkyl, alkenyl or aryl group, and X is a largely ionic bonded atom or group, and is preferably halogen, oxygen, sulfur, carboxylate, phenoxide, alkoxide, mercaptide, or cyanide. The bismuth compounds showing the unusual activity against bacteria are those having 1 or 2 atoms, or groups, joined to the bismuth atom by bonds having ionic characteristics. X may act as a bridging group or atom to provide his bismuth compounds which may be classified as substituted mono bismuth compounds and are within the scope of the present invention as defined herein. Various R and X groups may be cyclized or otherwise joined. The amount of the bismuth compound effective in a given application is dependent upon a number of factors which include the substrate to be protected, the method of application, the degree of protection desired, the bismuth compound utilized, the environment, etc. The bismuth compounds have proven to be effective against a wide spectrum of bacteria including gram negative and gram positive bacteria. They are particularly effective against gram negative bacteria. They are also effective against fungi.

Of the pentavalent organo bismuth compounds useful in this invention, those in which R is a monocyclic aryl, as exemplified by phenyl, monoand polychlorophenyls, tolyl, lower alkoxyphenyls and xylyl, are preferred. Of the monoand diorganic trivalent bismuth compounds those in which R is a monocyclic aryl are also preferred. Of those compounds in which the R group is an alkyl, those having less than 19 carbon atoms in the chain, and particularly those having from 3 to 8 carbon atoms are of most interest. These bismuth compounds in which X is a halogen or a carboxylate show greatest promise. The preferred compounds include: triphenylbismuth dihydroxide, triphenylbismuth dichloride, triphenylbismuth diacetate, triphenylbismuth disalicylate, diphenylbismuth chloride, diphenylbismuth acetate, diphenylbismuth sa- 1icylate,phenylbismuth dichloride, phenylbismuth diacetate, phenylbismuth disalicylate, diphenylbismuth lauryl- 3,239,411 anted Mar. 8, 1966 mercaptide, triphenylbismuth dibenzoate, phenylbismuth oxide, dibutylbismuth chloride, octylbismuth diacetate, dioctylbismuth o-phenylphenate.

The methods of this invention may be carried out by applying the bismuth compounds to the surface of -the material to be protected and/or admixing the bismuth compounds with the material to be protected during the fabrication of said material. The bismuth compounds may be used per se, particularly when they are incorporated into the material during preparation or fabrication. Many materials, and particularly fibrous products such as textiles, may be treated by applying the bismuth compound to the surface by dipping, padding, spraying, etc. They may be used in the form of a bactericidal and/or fungicidal composition in which the bismuth compound is the active component or one of the active components. Liquid compositions may be utilized in which the bismuth compound is dissolved and/or suspended in a solvent. Solid compositions may be utilized in which the bismuth compound is mixed with a carrier (or diluent). The carrier may be inert, such as talcs, clays, diatomaceous earth, flours, etc., or it may have activity such as that shown by the quaternary ammonium compounds. The liquid formulations of the emulsion type will often include a dispersion agent such as the anionic, cationic or nonionic surface active agents. To obtain fungicidal and/or bactericidal composition having an extremely broad spectrum of activity, the bismuth compounds may be formulated with other active materials such as the triorganotins, pentachlorophenol, copper-S-quinolinolate, bisphenols, o-phenylphenol, polybrominated salicylanilides, and metal (zinc) dialkyl dithiocarbamates. Illustrative of the compositions useful for carrying the active bismuth compound are Examples 1-4.

Example 1.Aer0s0l composition Parts by weight Tributyltin oxide 0.02 Triphenylbismuth dichloride 0.02 Toluene 15.00 Fluorohydrocarbon gaseous propellant 84.96 Example 2.Liquid composition Phenyloismuth disalicylate 1 Water 8 Acetone 2 Lauryl dimethylbenzylammonium chloride (50%in water) 10 Trisodium salt of N-hydroxyethyl-ethylenediamine triacetic acid 0.4 Toluene 3 Example 3.-Emulsion composition Tripropyltin acetate 0.02 Diphenylbismuth acetate 0.02 Toluene 15 Non-ionic surfactants 20 Water Balance Example 4.-S0lid composition Diatomaceous earth 80 v Triphenylbismuth dihydroxide 20 protected in the can and also after application. Typical paints include interior and exterior vinyl latex and alkyd paints, the older non-synthetic fiat natural paints, the acrylics, and the vinyls, and anti-fouling paints such as the acrylic and the vinyl varities thereof. The bismuth compounds are also useful in preserving adhesives; in secondary oil recovery processes; in paper mill slime control processes; and in methods of controlling Staphyloccus aureus in hospitals. They may be a useful and active component of detergent santiziers and may be used for this and other purposes in the form of an aerosol material. They may also be used to protect plants and other growth against micro-organism (largely fungi) attack. Illustrative of resistant paint compositions are noted micro-organisms. In each example the compound was tested using the Agar Diffusion Test, as follows: The test compounds were diluted in acetone to obtain the following stock solutions: 5, 2.5, 1.25, 0.63, 0.31%. Filter paper discs, 10 mm. in diameter, were dipped in the test solution and the solvent then allowed to evaporate. AATCC Bacteriostasis agar, held at 45 C., was inoculated to 1% with an 18-24 hours nutrient broth culture of Staph. aureus or Escherichia cali. The seeded agar was distributed at the rate of 15 ml./l cm. pctri dish and allowed to solidify. The treated filter paper discs were placed on the seeded agar. Then the plates were incubated at 37 C. for 48 hours. Inhibition was determined by a zone or halo adjacent to the treated disc.

Examples 7.

Exa1nple5 Acr ylic ti-f li i t Example 15.Z0nes of inhibition in mm.

Parts by Weight Percent solu- S. aurcus E. coli Titanium dioxide 160 Aluminum silicate 48 T 1 my th u 9 5 5 2 r1) ien isinn 101 on e... 5. Talc 12 1 y L 5 1 Methyl methacrylate-butyl methacrylate 0.63 5 1 copolymer (40% in thinner) 433 8: 8 Mineral spirits 148 25 0.08 o Dibutylbismuth acetate 50 g: 2 8

2 Example 6.Vinyl anti-fouling paint 01 0 0 Titanium dioxide 150 Partial. Bentonite 14 2 Partial zone. Tricresyl phosphite 10 Vinyl chloride-vinyl acetate copolymer Example 16 resin 102 Tohwne 223 Percent solu- S.aureu.s E. coli Methyl isobutyl ketone 295 tron mm. mm. Triphenylbismuth dichloride Phenylbismuth dichloride 35 Triphenylbismuth dichloride... g Example 7.-F lat interior paint g Titanium-calcium pigment 625 8 Calcium carbonate 100 Magnesium silicate 25 Ester gum Solution nonwolatlle 111 Example Z7.Z0nes of inhibition in mm.

mineral spirits) 3O Bqdled Fi O11 200 Percent solu- S. aureus E. coli Mineral spirits 167 40 tion mm. mm. Cobalt naphthanate (6% Co) 1 Lead naphthanate (24% Pb) 2 Phonylbismuth dichloride 5 15 0 Phenylbismuth dilaurylmercaptide 6 i12 g In each of Examples 8-14, tests are reported showing 13 6 the activity of the bismuth compounds against noted microorganisms, using the potent and toxic phenylmercury acetate as a standard. In each example, a series Example 18 of tests were carried out when the compound was placed within a nutrient broth in amount of 500, 250, 125, 63, mm Solu. gamma Eco 31, 16, 8, 4 and 2 parts per million (p.p.m.). Each 11911 broth was innoculated with the test organism and the broth incubated at 37 C. for two days. The organism growth Plwllylblsmuthdlchloflde %g 1 was visually observed. The broth containing the mini- 13 7 mum concentration which caused complete inhibition 60 13 5 of the growth of the organism is tabulated.

Staph. Aerobactar Pseudo- Examplc Compound aurcus, arrogance, mo air 13.11111. ppm. IIET'LLQZILOSG,

p.p.m.

Triphenylbisrnuth dichloride 8 31 31 Triphenylbismuth sulfide (crude) 16 250 Triphenylbismuth diacetate 1 8 l6 Triphenylbismuth dimethacrylate. 1 31 G3 Diphenylbismuth chloride 2 4 4 Phenylbismuth dichloride 2 2 2 Phenylmercury acetate-. 0.5 4 8 In each of Examples 15-18, tests are reported showing the activity of the bismuth compounds against the In each of Examples l923, a urethane foam containing one of the bismuth compounds was tested against Staph.

aureus in the Agar Diffusion Test. tion and results follow:

The foam composi- Zone of in- Parts by hibition, 111m. 5

Example weight Polysiloxane Stannous soap. N-ethylmorpholine- Triethylene diamine In each of Examples 24-25, a flexible polyvinylchloride plastic containing the specified amount of triphenylbismuth dichloride was tested against Staph. aureus in the Agar Diffusion Test.

Parts by Zone of in- Example weight lubition, m.m

Stcaric acid 0. 25 Dioctylphthalate 50 Polyvinyl chloride resin (Med. molecular weight) Bariurn-cadmium salt stabilizer Triphenylbismuth dichlor e. Triphenylbismuth dichloride.

In each of Examples 2 6 and 27, polyvinyl chloride samples with the same formulation as in Examples 24 and 25, were prepared containing 1 part and 0.5 parts of triphenylbismuth dichloride respectively. They were tested for activity against fungi as follows: 1%" squares of the plastic, including a plastic control containing none of the bismuth compounds, were placed in petri dishes containing ml. of a mineral salt agar. The plastic squares were inoculated with 0.5 ml. of a mixed spore suspension of Aspergillus niger, Aspergillus flavus, Trichoderma sp., and Penicillium piscarium. The inoculated samples were incubated at 86 F. for 14 days and then visually (and microscopically) examined for fungal growth. There was no growth on the samples prepared With the noted amounts of the bismuth compound. The plastic control exhibited moderate growth.

The following compounds are given as further examples of bismuth compounds employed in the com- .positions and methods of the invention and it will be understood that such compounds are used in place of the various compounds specifically shown in the foregoing examples.

Triphenylbismuth sulfide Triphenylbismuth diacetate Triphenylbismuth dimethacrylate Triphenylbismuth oxide Triphenylbismuth difluoride Triphenylbismuth dibromide Triphenylbismuth dihydroxide Triphenylbismuth (hydroxy)chloride Triphenylbismuth (chloro)acetate Triphenylbismuth dicyanide Trianisylbismuth dichloride Tribromophenylbismuth dichloride Trichlorophenylbismuth dichloride Tri-a-naphthylbismuth dichloride Trinitrophenylbismuth dichloride Tritolylbismuth dichloride Trixylylbismuth dibrornide Tribiphenylbismuth dichloride Di-phenyl-p-tolybisrnuth dichloride Tri-p-tolybismuth diacetate Triphenylbismuth dibenzoate Triphenylbismuth mercaptopropionate Tri-p-tolylbismuth dibenzoate Tri-o-tolybisrnuth disalicylate -C H Triphenylbismuth disalicylate Triphenylbismuth di-p-hydroxybenzoate Triphenylbismuth di-p-aminobenzoate Triphenylbismuth diap-aminobenzoate 2CH COCH Triphenylbismuth dichloroacetate Triphenylbismuth ditartrate Triphenylbismuth diphenoxide Triphenylbismuth dilaurylmercaptide Triphenylbismuth dibutoxide Tritolylbismuth di-o-phenylphenate Tritolylbismuth S,S'-bis isooctylmercaptoacetate Tritolylbismuth diethoxide Octylbismuth sulfide Butylbismuth sulfide Dibutylbismuth acetate Butylbismuth dibenzoate Dibutylbismuth methacrylate Butylbismuth diacrylate Dibutylbismuth phenate Butylbismuth mercaptopropionate Dibutylbismuth laurylmercaptide Dibutylbismuth isooctylme rcaptoacetate Butylbismuth bis-o-phenylphenate Diphenylbismuth chloride Di-p-chlorophenylbismuth chloride Di-p-chlorophenylbismuth bromide Di-p-chlorophenylbismuth iodide Diphenylbismuth chloride Diphenylbismuth iodide Diphenylbismuth cyanide Diphenylbismuth hydroxide Diphenylbismuth thiocyanate Di-p-tolylbismuth chloride Dicyclohexylbismuth chloride Cyclopentylbismuth diacetate Vinylphenylbismuth chloride Phenylbismuth dibromide P-Chlorophenylbismuth dibromide P-Tolylbismuth dichloride Diethylbismuth bromide Dibutenylbismuth chloride Diallylbismuth acetate Dimethylbismuth chloride Dimethylbismuth hydroxide Methylbismuth dichloride Methylbismuth oxide Butylbismuth sulfide Butylbismuth oxide Ethylbismuth dichloride Dibutylbismuth cyanide Those skilled in the art will appreciate that other organobismuth compounds as defined herein can be employed in the compositions and methods of the invention to protect a wide variety of materials and living organisms that are susceptible to attack by micro-organisms.

As many embodiments of this invention may be made without departing from the spirit and scope thereof, it is to be understood that the invention includes all such modifications as come within the scope of the appended claims.

What is claimed is:

1. A method for protecting a medium susceptible to attack by fungi and bacteria which comprises applying to the locus to be protected an effective amount of a bismuth compound selected tfrom the oup consisting of R' BiX and R BiX wherein n i to 2, X is selected from the group consisting of halogen, oxygen, s fur, carboxylate, phenoxide, alkoxide, mercaptidFand cyanide, R is an aryl, and R is selected fromthe group consisting of alkyl, cycloalkyl, alkenyl, and aryl.

2. The method of claim 1 wherein the bismuth compound is triphenylbismuth dihydroxide.

3. The method of claim 1 wherein the bismuth compound is triphenylbismuth dichloride.

4. The method .of claim 1 wherein the bismuth compound is triphenylbismuth diacetate.

5. The method of claim 1 wherein the bismuth compound is diphenylbismuth chloride.

6. The method of claim 1 wherein the bismuth compound is diphenylbismuth acetate.

7. The method of claim 1 wherein the bismuth compound is phenylbismuth dichloride.

8. The method of claim 1 wherein the bismuth compound is phenylbismuth diacetate.

9. The method of claim 1 wherein the bismuth compound is diphenylbismuth laurylmercaptide.

10. The method of claim 1 wherein the bismuth compound is diphenylbismuth salicylate.

11. The method of claim 1 wherein said bismuth compound is admixed with a micro-biologically active triorganotin compound.

12. The method of claim 11 wherein said mixture of organometal compounds is admixed with a surface-active agent.

13. The method of claim 11 wherein said mixture .of organometal compounds is admixed with a quaternary ammonium salt.

14. A fungi and bacteria resistant paint comprising a paint composition and an efiective amount of a bismuth compound selected from the group consisting of R' BiX and R BiX wherein n is 1 to 2, X is selected from the group consisting of halogen, oxygen, sulfur, carboxylate, phenoxide, alkoxide, mercaptide and cyanide, R is an aryl, and R is selected from the group consisting of alkyl, cycloalkyl, alkenyl, and aryl.

15. The resistant paint composition of claim 14 in which the paint is a marine anti-fouling paint.

16. A fungi and bacteria resistant plastic material comprising a plastic composition and an effective amount of a bismuth compound selected from the group consisting of R BiX and R BiX wherein n is 1 to 2, X is selected from the group consisting of halogen, oxygen, sulfur, carboxylate, phenoxide, alkoxide, mercaptide and cyanide, R' is an aryl, and R is selected from the group consisting of alkyl, cycloalkyl, alkenyl, and aryl.

17. The plastic material of claim 16 in which the plastic is a urethane.

18. A fungi and bacteria resistant paper comprising the paper and an effective amount of a bismuth com pound selected from the group consisting of R' BiX and R BiX wherein n is 1 to 2, X is selected from the group consisting of halogen, oxygen, sulfur, carboxylate, phenoxide, alkoxide, mercaptide and cyanide, R is an aryl, and R is selected from the group consisting of alkyl, cycloalkyl, alkenyl, and aryl.

19. A fungi and bacteria resistant cloth comprising the cloth and an efiective amount of a bismuth compound selected from the group consisting of R' BiX and R BiX wherein n is 1 to 2, X is selected from the group consisting of halogen, oxygen, sulfur, carboxylate, phenoxide, alkoxide, mercaptide and cyanide, R is an aryl, and R is selected from the group consisting of akyl, cycloalkyl, alkenyl, and aryl.

20. A bacteristatic aerosol composition comprising a carrier, a propellant and. as the active component, a bismuth compound selectedfrom the group consisting of R BiX and R BiX wherein n is 1 to 2, X is selected from the group consisting of halogen, oxygen, sulfur, carboxylate, phenoxide, alkoxide, mercaptide and cyanide, R is an aryl, and R is selected 'from the group consisting of alkyl, cycloalkyl, alkenyl, and aryl.

21. A method of treating a hospital to minimize the incidence of Staph. aureus which comprises applying to filters, room surfaces, and cloth, an efiective amount of a bismuth compound selected from the group tgnsisting of R BiX and R BiX wherein n is 1.102, X is selected from the group consisting of halogen, oxygen, sulfur, carboxylate, phenoxide, alkoxide, mercaptide and cyanide, R is an aryl, and R is selected from the group consisting of alkyl, cycloalkyl, alkenyl, and aryl.

22. A bactericidal composition comprising a bismuth compound selected from the group consisting of R' BiX and R BiX wherein n is 1 to 2, X is selected from the group consisting of halogen, oxygen, sulfur, carboxylate, phenoxide, alkoxide, mercaptide and cyanide, R is aryl, and R is selected from the group consisting of alkyl, cycloalkyl, alkenyl, and aryl, in admixture with a microbiologically active triorganotin compound.

UNITED STATES PATENTS References Cited by the Examiner 2,113,567 4/1938 Andersen 26013 2,114,012 4/1938 Andersen 260-13 2,423,262 7/1947 Sowa 167-30 2,555,114 5/1951 ByWater 260-433 OTHER REFERENCES Coates, Organo-Metallic Compounds, John Wiley and Sons, Inc., New York, 1956, pages 214 and 227-232.

Gilman et al., Chem. Review, volume 30, 1942. (pp. 300-307 and 312).

JULIAN S. LEVITI, Primary Examiner.

LEWIS GOTTS, Examiner. 

1. A METHOD FOR PROTECTING A MEDIUM SUSCEPTIBLE TO ATTACK BY FUNGI AND BACTERIA WHICH COMPRISES APPLYING TO THE LOCUS TO BE PROTECTED AN EFFECTIVE AMOUNT OF A BISMUTH COMPOUND SELECTED FROM THE GROUP CONSISTING OF R''3BIX2 AND RNBIX3-N, WHEREIN N IS 1 TO 2, X IS SELECTED FROM THE GROUP CONSISTING OF HALOGEN, OXYGEN, SULFUR, CARBOXYLATE, PHENOXIDE, ALKOXIDE, MERCAPTIDE AND CYANIDE, R'' IS AN ARYL, AND R IS SELECTED FROM THE GROUP CONSISTING OF ALKYL, CYCLOALKYL, ALKENYL, AND ARYL. 